Comparison of the results of sclerotherapy of esophageal varices using a rigid esophagoscope and fiber-optics esophagoscope

The authors compared the results of 20 emergency and 100 elective varicosclerotisations with rigid esophagoscope and the same number of obliterations with the use of esophagofiberoscope. Haemorrhage was stopped in 90% of patients injected through the rigid esophagoscope and in 80% of patients in whom esophagofiberoscope was used. Hospital mortality rate in patients with bleeding esophageal warices was 25% in both groups. Complications were seen in 4.2% of procedures carried out with the rigid esophagoscope, and 5.8% of obliterations with esophagofiberoscope. The authors recommend rigid esophagoscope for emergency sclerotherapy and for the initial 2-3 series of injections in patients with large varices. Esophagofiberoscope is prefered in case of repeated, elective varicosclerotisations, first injections and recurrence of esophageal varices following obliterative therapy.     

Mechanics and hemodynamics of esophageal varices during peristaltic contraction

Our hypothesis states that variceal pressure and wall tension increase dramatically during esophageal peristaltic contractions. This increase in pressure and wall tension is a natural consequence of the anatomy and physiology of the esophagus and of the esophageal venous plexus. The purpose of this study was to evaluate variceal hemodynamics during peristaltic contraction. A simultaneous ultrasound probe and manometry catheter was placed in the distal esophagus in nine patients with esophageal varices. Simultaneous esophageal luminal pressure and ultrasound images of varices were recorded during peristaltic contraction. Maximum variceal cross-sectional area and esophageal luminal pressures at which the varix flattened, closed, and opened were measured. The esophageal lumen pressure equals the intravariceal pressure at variceal flattening due to force balance laws. The mean flattening pressures (40.11 +/- 16.77 mmHg) were significantly higher than the mean opening pressures (11.56 +/- 25.56 mmHg) (P < or = 0.0001). Flattening pressures >80 mmHg were generated during peristaltic contractions in 15.5% of the swallows. Variceal cross-sectional area increased a mean of 41% above baseline (range 7-89%, P < 0.0001) during swallowing. The peak closing pressures in patients that experience future variceal bleeding were significantly higher than the peak closing pressures in patients that did not experience variceal bleeding (P < 0.04). Patients with a mean peak closing pressure >61 mmHg were more likely to bleed. In this study, accuracy of predicting future variceal bleeding, based on these criteria, was 100%. Variceal models were developed, and it was demonstrated that during peristaltic contraction there was a significant increase in intravariceal pressure over baseline intravariceal pressure and that the peak intravariceal pressures were directly proportional to the resistance at the gastroesophageal junction. In conclusion, esophageal peristalsis in combination with high resistance to blood flow through the gastroesophageal junction leads to distension of the esophageal varices and an increase in intravariceal pressure and wall tension.     

Crural diaphragm inhibition during esophageal distension correlates with contraction of the esophageal longitudinal muscle in cats

Esophageal distension causes simultaneous relaxation of the lower esophageal sphincter (LES) and crural diaphragm. The mechanism of crural diaphragm relaxation during esophageal distension is not well understood. We studied the motion of crural and costal diaphragm along with the motion of the distal esophagus during esophageal distension-induced relaxation of the LES and crural diaphragm. Wire electrodes were surgically implanted into the crural and costal diaphragm in five cats. In two additional cats, radiopaque markers were also sutured into the outer wall of the distal esophagus to monitor esophageal shortening. Under light anesthesia, animals were placed on an X-ray fluoroscope to monitor the motion of the diaphragm and the distal esophagus by tracking the radiopaque markers. Crural and costal diaphragm electromyograms (EMGs) were recorded along with the esophageal, LES, and gastric pressures. A 2-cm balloon placed 5 cm above the LES was used for esophageal distension. Effects of baclofen, a GABA(B) agonist, were also studied. Esophageal distension induced LES relaxation and selective inhibition of the crural diaphragm EMG. The crural diaphragm moved in a craniocaudal direction with expiration and inspiration, respectively. Esophageal distension-induced inhibition of the crural EMG was associated with sustained cranial motion of the crural diaphragm and esophagus. Baclofen blocked distension-induced LES relaxation and crural diaphragm EMG inhibition along with the cranial motion of the crural diaphragm and the distal esophagus. There is a close temporal correlation between esophageal distension-mediated LES relaxation and crural diaphragm inhibition with the sustained cranial motion of the crural diaphragm. Stretch caused by the longitudinal muscle contraction of the esophagus during distension of the esophagus may be important in causing LES relaxation and crural diaphragm inhibition.     

Significance of endoscopic biopsy and cytology in the diagnosis of esophageal squamous cell carcinoma

We have tested the role and significance of histology combined with cytology in the diagnosis of esophageal squamous cell carcinomas. Biopsy specimens and samples for cytological smear were taken by a fiberoptic flexible endoscope. In order to minimise the loss of biological sample, the residue from the brush was removed with rinsing fluid. From 1973 to 2005 we examined 820 patients with squamous cell carcinoma of the esophagus. Endoscopic biopsy yielded positive result in 97.2%. Cytology performed in 724 patients turned out to be positive in 90.3%. Both examinations were conducted in 648 patients (79%), and yielded positive result in 572 patients (88.3%). Negative biopsy result was obtained in 22 patients, however, 14 of them had positive cytological diagnosis. Both biopsy and cytology were negative in 8 cancer patients (1%). No complication was observed with either diagnostic technique. In our material cancer was diagnosed in 776 patients by histology. However, in a further 14 of 22 patients with negative histology, cancer was detected by cytology. This means that the presence of cancer was also confirmed on the basis of morphological features in 790 cases, i.e. in 96.3% of the patients. Our results show that the combined use of biopsy and cytology in malignant tumours yields high diagnostic accuracy. Since abrasion exfoliate cytology is a quick and useful diagnostic measure it should be a routine examination in the evaluation of abnormal changes in the esophageal mucosa. The examination of the rinsing fluid of the sampling brush, introduced by us, yielded additional diagnostic information.     

Mechanisms of esophageal cancer development in Brazilians

Esophageal cancer represents one of the most common and lethal cancers around the World. Some areas of South America, including parts of Brazil, present the highest incidence of the disease in the West. The main etiological factors that have been associated with the disease in Brazil are alcohol consumption, tobacco smoking and, in the South, consumption of hot maté. Nitrosamines are the only carcinogens capable of inducing tumors in the esophagus of experimental animals, with the rat being the most susceptible species, mainly due to tissue specific metabolic activation by CYP enzymes. Studies of CYP2A expression in the esophagus of rodents suggest an association between CYP2A expression and esophageal susceptibility to tumor induction. CYP2A6 and CYP2E1, the main enzymes to activate nitrosamines in humans, are the only carcinogen activating CYP enzymes to be expressed in the esophagus of Brazilians. Patients who presented high levels of CYP2A6 expression could activate nitrosamines at rates comparable to the rat. This expression profile is different from those present in French patients. We investigated 34 Brazilian patients regarding the risk associated with polymorphisms in drug metabolizing enzymes and TP53 mutations. A GSTP1 polymorphism presented a clear risk to white and non-white patients to develop esophageal cancer. GSTM1 null polymorphism also seemed to be associated with an increased risk. CYP2A6, CYP2E1, SOD2, and GSTT1 polymorphisms were not associated with an increased risk of esophageal cancer. TP53 mutations occurred mostly in exon 7, differing from the mutation profile found in the IARC database. The preliminary results obtained with polymorphisms of drug metabolizing enzymes and TP53 mutations need to be confirmed in a larger number of samples in order to compare the mechanisms of esophageal cancer development in Brazilians with that of other populations.     

Novel device to sample the esophageal microbiome-the esophageal string test

A growing number of studies implicate the microbiome in the pathogenesis of intestinal inflammation. Previous work has shown that adults with esophagitis related to gastroesophageal reflux disease have altered esophageal microbiota compared to those who do not have esophagitis. In these studies, sampling of the esophageal microbiome was accomplished by isolating DNA from esophageal biopsies obtained at the time of upper endoscopy. The aim of the current study was to identify the esophageal microbiome in pediatric individuals with normal esophageal mucosa using a minimally invasive, capsule-based string technology, the Enterotest?. We used the proximal segment of the Enterotest string to sample the esophagus, and term this the "Esophageal String Test" (EST). We hypothesized that the less invasive EST would capture mucosal adherent bacteria present in the esophagus in a similar fashion as mucosal biopsy. EST samples and mucosal biopsies were collected from children with no esophageal inflammation (n?=?15) and their microbiome composition determined by 16S rRNA gene sequencing. Microbiota from esophageal biopsies and ESTs produced nearly identical profiles of bacterial genera and were different from the bacterial contents of samples collected from the nasal and oral cavity. We conclude that the minimally invasive EST can serve as a useful device for study of the esophageal microbiome.     

Targeting chemokine pathways in esophageal adenocarcinoma

Esophageal adenocarcinoma (EAC) is one of the fastest growing malignancies in the US and needs newer therapeutic and diagnostic strategies. Chronic inflammation plays a role in the pathogenesis of EAC and contributes to the dysplastic conversion of normal esophageal epithelium to Barrett's esophagus and frank adenocarcinoma. Chemokines play important roles in mediating inflammation and recent evidence implicates these ligands and their receptors in the development and spread of various tumors. We demonstrated that the chemokines IL8, CXCL1 and CXCL3 are significantly overexpressed during esophageal carcinogenesis and accompanied by amplification and demethylation of the chr4q21 gene locus. We also demonstrated that IL8 levels can be detected in serum of patients with EAC and can serve as potential biomarkers. We now demonstrate that inhibition of IL8 receptor, CXCR2, leads to decreased invasiveness of esophageal adenocarcinoma derived cells without affecting cellular proliferation. Taken together, these studies reveal the important roles that chemokines play in development of esophageal cancer and demonstrate that these pathways can serve as potential therapeutic targets.     

The problem of the acquired short esophagus; report of 18 patients

A shortened esophagus is probably acquired, rather than congenital, in the great majority of cases. The process by which the shortening develops, as described by Allison and his coworkers, begins with esophageal hiatal hernia, followed by esophagitis caused by the irritation of acids from the stomach, then recurrent ulceration and healing which forms scar tissue which little by little shortens the esophagus. Obesity and relaxation of the supporting musculotendinous structures which accompany advancing years probably are contributory factors in production of esophageal hiatal hernia. Fifteen of a series of 18 patients noted the onset of symptoms on or after the age of 45. Roentgen examination of the esophagus and stomach is indispensable in establishing a diagnosis of acquired short esophagus. Esophagoscopic examination is even more important. In some cases endoscopic differentiation between acute inflammation and carcinoma is difficult. In such circumstances examination of a biopsy specimen taken from the gastric mucosa immediately distal to the area of inflammation or stricture may be helpful. Results in eight patients with advanced esophageal shortening and stricture who were treated conservatively indicate that this should be tried before surgical treatment is considered. For patients with esophageal hiatal hernia accompanied by shortening of the esophagus that is just beginning to produce symptoms, early repair is indicated, since the condition is progressive and the surgical problem is much simpler in the early stages.     

THE PROBLEM OF THE ACQUIRED SHORT ESOPHAGUS—Report of 18 Patients

A shortened esophagus is probably acquired, rather than congenital, in the great majority of cases. The process by which the shortening develops, as described by Allison and his coworkers, begins with esophageal hiatal hernia, followed by esophagitis caused by the irritation of acids from the stomach, then recurrent ulceration and healing which forms scar tissue which little by little shortens the esophagus.Obesity and relaxation of the supporting musculotendinous structures which accompany advancing years probably are contributory factors in production of esophageal hiatal hernia. Fifteen of a series of 18 patients noted the onset of symptoms on or after the age of 45.Roentgen examination of the esophagus and stomach is indispensable in establishing a diagnosis of acquired short esophagus. Esophagoscopic examination is even more important. In some cases endoscopic differentiation between acute inflammation and carcinoma is difficult. In such circumstances examination of a biopsy specimen taken from the gastric mucosa immediately distal to the area of inflammation or stricture may be helpful.Results in eight patients with advanced esophageal shortening and stricture who were treated conservatively indicate that this should be tried before surgical treatment is considered. For patients with esophageal hiatal hernia accompanied by shortening of the esophagus that is just beginning to produce symptoms, early repair is indicated, since the condition is progressive and the surgical problem is much simpler in the early stages.     

内镜下硬化剂和套扎治疗食管静脉曲张术后对门脉高压性胃病和胃底静脉曲张的影响

目的:探讨食管静脉曲张(EV)采用内镜下套扎术(EVL)和硬化剂(EVS)治疗对患者近远期并发胃底静脉曲张(GV)以及门脉高压性胃病(PHG)并发症的影响。方法:抽选我院肝硬化上消化道出血后接受内镜下治疗的患者97例为研究对象,其中19例予以内镜下EVS治疗,78例行内镜下EVL治疗,随访1年,观察治疗3个月、6个月、1年后并发GV、PHG的近远期概率。结果:治疗3个月后,本组患者GV、PHG等并发症的发生率为17.5%(17/97)、39.2%(38/97),与治疗前比较差异无显著性(P0.05);治疗6个月后,本组患者GV、PHG等并发症的发生率为32%(31/97)、70.1%(68/97),与治疗前相比,并发人数显著增加(P0.05);治疗1年后,GV、PHG的发生率为42.3%(41/97)、88.7%(86/97),并发人数显著高于治疗前(P0.05)。结论:内镜下EVS、EVL治疗在消退食管曲张静脉和良好地控制出血的同时,还可增加PHG、GV的并发几率,值得临床重视预防。     

Cytopathology of the esophagus. An overview of esophageal cytopathology in China

Carcinoma of the esophagus is the most common malignancy in many parts of China. In an attempt to control it by early diagnosis, the balloon sampling technique was developed approximately 20 years ago. This technique is now widely used in China and is accepted as a diagnostic method by WHO. Up to 1979, more than 500,000 people were examined in China. It is routinely used for differentiation between benign and malignant lesions in the esophagus, with an accuracy in the range of 90%. In mass surveys, 73.8% of the cancers detected have been carcinoma in situ and minimally invasive carcinomas. Dysplasias have been shown to progress to invasion by cytologic studies. The utilization of this technique has made possible epidemiologic studies and, thereby, coordination of etiologic research in esophageal cancer. Detection rates of early esophageal cancer by cytologic studies are more accurate than are those with either endoscopic or radiologic methods. The instruments and technique for balloon sampling of esophageal lesions are described, as are the cellular cytomorphology and the diagnostic cytologic criteria applicable to the samples obtained.     

Use of the esophageal balloon in the diagnosis of carcinomas of the head, neck and upper gastrointestinal tract

A study was undertaken to demonstrate the safety, efficacy and value of esophageal balloon cytology in the diagnosis of esophageal lesions and as a tool in screening a high-risk patient population. The sampling was performed 110 times on 96 patients, 11 with known obstructive carcinoma of the esophagus and 85 thought to be at risk for esophageal cancer: 74 with treated or untreated cancer of the head and neck area and 11 with dysphagia or other findings requiring clarification. The method was well tolerated by the patients, and the cytologic smears were of excellent quality. Malignant or suspicious cells were found in smears from 7 to 11 patients with documented esophageal cancer and in 7 of 85 patients believed to be at risk. In the latter group there were three unsuspected recurrent cancers of the oropharyngeal region and one unsuspected carcinoma in situ of the esophagus. There were no false-suspicious or false-positive results. This noninvasive technique of esophageal cytology obviously deserves additional trials as an adjunct in the diagnosis of carcinoma of the head and neck and upper gastrointestinal tract, especially in high-risk patients.     

Serial fine needle cytology in the diagnosis of esophageal cancer

OBJECTIVE: To describe a method of registering local spread of cancer in the esophageal wall through serial endoscopic fine needle aspiration (FNA), to evaluate FNA as a diagnostic tool as compared to histologic biopsies and brush cytology, and to investigate cytologic appearances of aspirates and correlate them with survival STUDY DESIGN: Fifty-two patients with esophageal cancer were investigated with serial FNA every second centimeter from the upper esophageal sphincter aborally down to the level of macroscopic tumor. Histologic biopsies and brush cytologies were then performed. RESULTS: Of investigated cases, 33% showed malignant or suspect malignant cells from macroscopic tumor, at > or = 4 cm orally, as did 3 of 12 patients at 14 cm. FNA was more sensitive than brush cytology in establishing the diagnosis. A high ratio between the numbers of benign and malignant cells in aspirates from gross tumor tissue correlated with shorter survival (P < .03). CONCLUSION: Serial FNA can demonstrate local microscopic tumor spread in the wall of the esophagus in vivo in esophageal cancer patients. FNA is also a useful adjunct in establishing the diagnosis. Finally, evaluations of tumor cytology may have prognostic value.     

Safrole-DNA adducts in tissues from esophageal cancer patients: clues to areca-related esophageal carcinogenesis

Epidemiological studies have demonstrated that areca quid chewing can be an independent risk factor for developing esophageal cancer. However, no studies are available to elucidate the mechanisms of how areca induces carcinogenesis in the esophagus. Since the areca nut in Taiwan contains a high concentration of safrole, a well-known carcinogenic agent, we analyzed safrole-DNA adducts by the 32P-postlabelling method in tissue specimens from esophageal cancer patients. In total, we evaluated 47 patients with esophageal cancer (16 areca chewers and 31 non-chewers) who underwent esophagectomy at the National Taiwan University Hospital between 1996 and 2002. Of the individuals with a history of habitual areca chewing (14 cigarette smokers and two non-smokers), one of the tumor tissue samples and five of the normal esophageal mucosa samples were positive for safrole-DNA adducts. All patients positive for safrole-DNA adducts were also cigarette smokers. Such adducts could not be found in patients who did not chew areca, irrespective of their habits of alcohol consumption or cigarette smoking (p<0.001, comparing the areca chewers with non-chewers). The genotoxicity of safrole was also tested in vitro in three esophageal cell lines and four cultures of primary esophageal keratinocytes. In two of the esophageal keratinocyte cultures, adduct formation was increased by treatment with safrole after induction of cytochrome P450 by 3-methyl-cholanthrene. This paper provides the first observation of how areca induces esophageal carcinogenesis, i.e., through the genotoxicity of safrole, a component of the areca juice.     

兔食管静脉曲张模型的建立

目的建立新西兰兔的食管静脉曲张模型,为下一步的临床研究提供可靠的小型动物模型。方法采用门静脉左支完全夹闭法造模,并通过外观、超声、胃镜等检查检验手段对造模结果加以评估。结果术后8周存活动物100%可见食管静脉曲张。结论通过门静脉左支夹闭法,基本可以建立兔食管静脉曲张模型。     

Replication study of PLCE1 and C20orf54 polymorphism and risk of esophageal cancer in a Chinese population

Esophageal cancer is one of the most aggressive cancers in the world. Recent large-scale genome-wide association studies (GWAS) reported that functional genetic variations in the phospholipase C epsilon gene (PLCE1) were strongly associated with risk of esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA) in Chinese population. For C20orf54 rs13042395 genotype and risk of esophageal cancer, the results were inconsistent. We conducted a replication case-control study to evaluate the genetic effects of these two functional single nucleotide polymorphisms (SNPs) on the development of esophageal cancer. A total of 380 cases and 380 controls were recruited for this study. The genotypes were determined by matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-ToF MS). The variant alleles of the functional polymorphism, PLCE1 rs2274223 SNP was associated with the increased risk of esophageal cancer [adjusted odds ratio (OR) = 1.95, 95 % confidence interval (CI) = 1.05-3.59 for PLCE1 rs2274223 GG vs. AA]. However, there was no significant association between the C20orf54 rs13042395 genotype and esophageal cancer risk (adjusted OR = 0.99, 95 % CI = 0.63-1.57 for C20orf54 rs13042395 TT vs. CC). Stratified analyses indicated a significantly increased risk of esophageal cancer associated with the PLCE1 rs2274223 AG genotype was more evident among females, younger patients and never drinkers, compared with the PLCE1 rs2274223 AA genotypes. Stratified analyses also indicated a significantly increased risk of esophageal cancer associated with the PLCE1 rs2274223 GG genotype was more evident among never smokers and never drinkers compared with the PLCE1 rs2274223 AA genotypes. These findings indicated that functional polymorphisms PLCE1 rs2274223 might contribute to esophageal cancer susceptibility.     

Simplified oesophageal transection for bleeding varices.

Thirty patients with bleeding oesophageal varices were treated by oesophageal transection using the SPTU gun. Any form of shunt was contraindicated in all the patients. Twelve operations were done as urgent procedures within 36 hours of haemorrhage. The overall operative mortality rate was 10%, and there were two late deaths during follow-up, which has so far extended from two months to two years. Three of the patients had recurrent bleeding, and residual varices were probably the source in two. There were no cases of portal systemic encephalopathy. Although the follow-up is too short to allow any definite conclusions, these early results suggest that oesophageal transection with the SPTU gun may be useful in the large proportion of patients in whom injection sclerotherapy, shunt surgery, or conservative treatment is inappropriate.     

Surgical indication in Schistosomiasis mansoni portal hypertension: follow-up from 1985 to 2001

The study had the objective to evaluate the benefits of surgical indication for portal hypertension in schistosomiasis patients followed from 1985 to 2001. Schistosoma mansoni eggs were confirmed by at least six stool examinations or rectal biopsy. Clinical examination, abdominal ultrasonography, and digestive endoscopy confirmed the diagnosis of esophageal varices. A hundred and two patients, 61.3% male (14-53 years old) were studied. Digestive hemorrhage, hypersplenism, left hypochondrial pain, abdominal discomfort, and hypogonadism were, in a decreasing order, the major signs and symptoms determining surgical indication. Among the surgical techniques employed, either splenectomy associated to splenorenal anastomosis or azigoportal desvascularization, esophageal gastric descompression and esophageal sclerosis were used. Follow-up of patients revealed that, independent on the technique utilized, a 9.9% of death occurred, caused mainly by digestive hemorrhage due to the persistence of post-treatment varices. The authors emphasize the benefits of elective surgical indication allowing a normal active life.     

Esophageal Adenocarcinoma and Its Rare Association with Barrett’s Esophagus in Henan,China

Incidence of esophageal adenocarcinoma (EAC) has increased sharply in Western Europe and United States over the past three decades. Nearly all cases of EAC in the west are thought to be associated with Barrett’s esophagus (BE) at the time of diagnosis. Regions in the Henan province of China have one of world’s highest incidences of esophageal cancer, yet recent temporal trends in the relative rates of EAC with respect to esophageal squamous-cell carcinoma (ESCC), as well as its association with Barrett’s esophagus (BE), have not been reported. In this report, we present large-scale longitudinal clinical and histological data on 5401 esophageal cancers (EC) patients diagnosed during the recent 10-year period (2002–2011) at Henan Cancer Hospital, China. All 217 esophageal adenocarcinoma (EAC) patients from these 5401 EC patients were examined to better understand the relationship between Barrett’s esophagus (BE) and EAC. We found that EAC was relatively rare and accounted for approximately 5% of all esophageal cancers each year during 2002–2011. There is no evidence of significant temporal trends in the rate of EAC relative to ESCC. Only 10 out of 217 (4.6%) EAC cases were detected to have any evidence of Barrett’s esophagus. This result raises the possibility of a different etiological basis for EAC in China motivating more detailed epidemiological, clinical and molecular characterization of EAC in China in order to better understand the neoplastic development of EAC.